Major Depressive Disorder

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

A version of this article first appeared on Medscape.com.

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

A version of this article first appeared on Medscape.com.

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

A version of this article first appeared on Medscape.com.

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Expanding suicide risk screening in primary care to identify patients at highest risk may help boost prevention efforts and make better use of health care resources, according to a new study.

Craig J. Bryan, PsyD, ABPP, with the department of psychiatry and behavioral health at Ohio State University Wexner Medical Center, Columbus, led the study, published online on Nov. 8, 2021, in Annals of Family Medicine.

The authors cited the urgency highlighted by statistics showing that, from 1999 to 2017, the U.S. suicide rate increased by more than 33% and was particularly high among military personnel and veterans.

Primary care offices are seen as a prime target for prevention efforts as nearly one-half of people who die by suicide in the United States visit a primary care office in the months before their deaths.

A common approach to screening for suicide risk has been to use the Patient Health Questionnaire–9 (PHQ-9). The first two questions assess the frequency of depressed mood and anhedonia in the past 2 weeks. If patients screen positive on those two questions, they are given the remaining seven questions.

A single item – question 9 – asks about how often a patient has “thoughts that you would be better off dead, or of hurting yourself in some way” during the past 2 weeks.

Yet, more that 95% of patients who screen positive on the PHQ-9 suicide risk question do not attempt or die by suicide, the authors noted.
 

Two methods tested for improving screening

Dr. Bryan and colleagues wanted to assess whether suicide risk screening could be improved in primary care and evaluated two methods.

One was to see whether using any of the other PHQ-9 items could be better than just using item 9 alone to identify the patients who were most likely to attempt suicide in the near future. Researchers found that method was not significantly beneficial. The second was to evaluate the performance of the 16 items on the Suicide Cognitions Scale (SCS), a questionnaire that asks patients to rate the extent to which they agree or disagree with statements that are commonly endorsed by suicidal people.

Patients who were eligible for medical treatment from the Department of Defense medical system were recruited from six large and small military primary care clinics across the United States from July 2015 to August 2018.

Patients answered questions on the PHQ-9 and 16 items from the SCS during routine primary care visits. Evaluators, who were blind to screening results, assessed postbaseline suicide attempts, interrupted attempts and aborted attempts by interviewing patients.

The study included 2,744 primary care patients, ranging from 18 to 89 years of age, with an average age of 40.
 

Adding at least one question may help

Researchers found that the accuracy of suicide risk screening using the PHQ-9 can be significantly improved by adding one or more questions from the SCS. Three items from SCS contributed most to meaningful improvements in identifying patients who went on to exhibit suicidal behaviors within 30-90 days of screening.

One question was item 16: “I don’t deserve to live another moment.”

Two SCS items improved specificity and positive predictive value without reducing sensitivity, the authors wrote. They are: “It is unbearable when I get this upset” (item 8) and “I can’t imagine anyone being able to withstand this kind of pain” (item 13).

“For example,” the authors wrote, “only 4.1% of patients who screened positive on the PHQ-9 suicide risk item 9 engaged in suicidal behavior within the next 30 days, but when the PHQ-9 suicide risk item 9 was combined with SCS item 13 (the best-performing SCS item), this percentage nearly doubled, to 7.6% of patients.”

Adding one of these SCS items to the PHQ-9 “could provide a simple, accessible, and low-cost method for more accurately identifying primary care patients who require more immediate clinical intervention,” the authors wrote.
 

Outside expert perspective

Meredith Williamson, PhD, a mental health diagnosis and psychotherapy expert and clinical assistant professor at Texas A&M University, Bryan, said that, though the SCS questions are valuable, neither they nor the PHQ-9 question get to the direct question of whether the person is likely to act on their thoughts and attempt or complete suicide.

“Someone with depression may have thought of wishing they were dead or wishing they weren’t here but that doesn’t always mean they necessarily want to kill themselves,” she said in an interview. “It’s our responsibility as providers to really clarify the meaning of that item.”

Dr. Williamson noted the PHQ-9 is a very accessible method to screen for depression in primary care settings and is a way to catch large numbers of people screening positive, but its shortcomings are well known and additional information is needed.

She said that, in her practice, if a patient screens positive on PHQ-9, clinicians ask more about their intentions, how frequently they occur and whether patients have developed a plan for killing themselves.

The challenge is that “we have yet to predict who is and who is not going to kill themselves.”

Dr. Williamson said she finds the Columbia-Suicide Severity Rating Scale a valuable tool used in research settings that looks at prior attempts and current desire to engage in an attempt in more detail.

“It doesn’t stop people from killing themselves, but helps to better understand their suicidal behavior,” she explained.

This project was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program. Dr. Williamson has no relevant financial disclosures. Dr. Bryan is a paid consultant to Oui Therapeutics and Neurostat Analytical Solutions. He is a principal of Anduril, which conducts training workshops and provides mental health consultation focused on suicide prevention and PTSD.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.

“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”

In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”

Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.

Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.

“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.

Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.

When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.

“These data motivate a systematic study of humoral immunity in the CSF of pediatric patients with COVID-19 and neuropsychiatric involvement and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
 

Potential of CNS autoimmunity

Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.

“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”

Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.

“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”

The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Telehealth is safe and effective for the treatment of borderline personality disorder (BPD) and may even have an edge over in-person treatment, new research suggests.

Courtesy Dr. Mark Zimmerman

Investigators compared BPD outcomes with therapy delivered in person and via telemedicine and found comparable reductions in depression, anxiety, and anger symptoms as well as improved overall well-being and mental health.

The results also suggest a telehealth advantage with significantly better patient attendance vs. patients treated in-person.

“We found a large effect size of treatment in both groups, as well as comparable levels of satisfaction with treatment, symptom reduction, and improved functioning, coping ability, positive mental health, and general well-being,” study investigator Mark Zimmerman, MD, professor of psychiatry and human behavior, Brown University, Providence, R.I., said in an interview.

The study was published online Nov. 8 in the Journal of Personality Disorders.
 

‘No other option’

Most previous research investigating telehealth has occurred in outpatient, individual treatment settings and has not examined telehealth-delivered group therapy or partial hospitalization, the authors noted.

“Until the pandemic, we were delivering care in person, but when the pandemic began, because of public safety recommendations, we knew that we could no longer continue doing so,” said Dr. Zimmerman, director of the outpatient division at the partial hospital program (PHP), Rhode Island Hospital.

“In switching to a telehealth platform, we were concerned about patient safety and acceptability of delivering care in that manner, especially with patients with BPD, which is associated with impulsive behavior, self-harm, and suicidal behavior, among other problems,” he said. However “we had no other option” than to utilize a telehealth delivery mode, since the alternative was to shut down the program.

The investigators were “interested in whether or not virtual treatment in an acute intensive setting, such as a PHP, would be as safe, acceptable, and effective as in-person treatment.”

The study was part of the ongoing work of the Rhode Island Methods to Improve Diagnostic Assessment and Services.
 

Additional safety measures

Treatment, consisting of an Acceptance and Commitment Therapy (ACT) treatment model – including intake assessments, individual therapy, psychiatric visits, and group therapy – was delivered by a multidisciplinary team via Zoom.

Dr. Zimmerman noted that the team implemented additional safety precautions, including having patients check in at the beginning of each day to indicate their location, not seeing patients who were out of state, and making sure all patients had a contact person.

In addition, beyond the therapist leading the group, another therapist was always available, overseeing groups and meeting one-on-one (virtually) with participants if they had been triggered by the group process and were highly distressed.

Patients were asked to complete a number of questionnaires, including the Clinically Useful Patient Satisfaction Scale (CUPSS) at the end of their intake session. The primary outcome measure was the Remission from Depression Questionnaire (RDQ-M).

The study was conducted between May 1 and Dec. 15 of 2020 and included 64 patients with BPD who were treated for the first time in the Rhode Island Hospital PHP. They were compared to 117 patients who participated in the in-person program during the same months in 2019.

Participant characteristics were similar – for example, three-quarters of the participants in both groups were female, and the mean age was 34 years.
 

‘Sea change’

Most patients in the telehealth and in-person groups reported being “very” or “extremely” satisfied with the initial evaluation (90% vs. 85.3%, c² = 0.74) and were hopeful that they would get better (85.8% vs. 82.1%, c² = 0.45).

Upon completion of the program, 100% of the in-person and 95.4% of the telehealth group indicated that they were “very” or “extremely” satisfied (c² = 4.62), and “under both telehealth and in-person treatment conditions, the patients significantly improved from admission to discharge on each of the RDQ-M subscales, with large effect sizes found for most of the subscales,” the authors reported.

There were significant differences between the groups in the average number of days of attendance and number of days missed.

A nonsignificantly higher proportion of patients completed the telehealth program, vs. the in-person program (68.8% vs. 59%, c² = 1.69).

In both programs, transfer to inpatient care and dissatisfaction-related withdrawal from the program were low (both < 2%). Notably, no patients attempted or completed suicide during treatment.

Virtual treatment is more convenient than in-person treatment, Dr. Zimmerman noted. “Some patients – generally those with medical or transportation issues – told us they otherwise would not have been able to participate [in the program] if treatment had been in person.”

He added, “My prediction is that 5 years from now, two-thirds to three-quarters of outpatient visits will be virtual because that is what the patients prefer – and although there will certainly be individuals who prefer in-person care, I think we’ve witnessed a sea change in how behavioral health care will be delivered.”
 

‘Game changer’

In an interview, Monica Carsky, PhD, clinical assistant professor of psychology in psychiatry and a senior fellow at the Personality Disorders Institute, Weill Cornell Medical College, New York, said the study has “a lot of valuable detail about how to set up a virtual PHP, which could guide any group wanting to try this.”

Dr. Carsky, who was not involved with the study, called it “a very important contribution to the research literature on efficacious treatment of BPD,” although it is not a randomized controlled trial.

“Adding more individual attention to the virtual group (e.g., having a co-host in the groups) seems as though it may be an important factor in dealing with the limitations of virtual treatment,” she noted.

However, she continued, “a limitation is that outcome assessment relied on self-administered questionnaires and did not include clinician rating scales, so the response may have been subject to the effects of social desirability bias.”

Courtesy Dr. Donald Black

Donald W. Black, MD, associate chief of staff for mental health at the Iowa City Veterans Administration Hospital, said in an interview that the pandemic has been a “game changer, as we have had to quickly adapt mental health programs to a virtual format.

“For the most part, they have been remarkably successful for a variety of conditions, and Zimmerman and colleagues now show this for BPD families,” said Dr. Black, who was not associated with the research.

No study funding was listed. The study authors, Dr. Carsky, and Dr. Black have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Brain beta rhythm predicts early and robust response to deep brain stimulation (DBS) for severe depression in new findings that could help optimize and personalize DBS treatment protocols, early research suggests.

In a small study, investigators found brief stimulation at the time of implantation of DBS leads induced a rapid and consistent decrease in beta power measured at the site of stimulation, which correlated with significant and sustained decrease in depressive symptoms.

“Patient by patient, the magnitude of the decrease in the left beta power could predict how well they were doing a week later,” study investigator Helen Mayberg, MD, founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai in New York, told this news organization.

The study was published online Nov. 3 in Translational Psychiatry.
 

Optimal targets identified

Eight adults with treatment-resistant depression underwent intraoperative electrophysiological recording at the time that bilateral DBS leads were implanted in the subcallosal cingulate (SCC).

Using patient-specific tractography models prior to surgery, the investigators identified the optimal target within the SCC for lead placement.

During surgery, 20 minutes of stimulation in the optimal tractography-defined targets was delivered, with no stimulation in the 4 weeks after surgery. Local field potentials (LFPs) – electrical signals between neurons deep in the brain – were simultaneously recorded during intraoperative stimulation.

One week after brief intraoperative stimulation, patient depression scores had declined by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS-17).

This early antidepressant response correlated with a decrease in the beta power recorded from the left hemisphere SCC. The correlation of symptom improvement with reduction in SCC beta power suggests that this electrophysiological finding is a “biomarker for treatment optimization,” the investigators note.

“This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients,” Dr. Mayberg said in a press release.

“Within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who showed larger changes then experienced greater relief from their depression in the week after surgery,” added Allison Waters, PhD, a co–first author on the study and electrophysiology core leader at Mount Sinai’s Nash Center.

It appears that the early decline in depressive symptoms is “partially but not completely lost” during a postoperative, one-month washout period, the researchers note.

In addition, it remains unknown whether intraoperative stimulation-induced changes in beta power are predictive of eventual sustained clinical response to chronic therapeutic SCC DBS for treatment-resistant depression.

To this point, however, chronic SCC DBS at the tractography-defined “optimal” locations led to a response rate of 88% (7 of 8) after 6 months of treatment, they report.
 

One step closer to precision psychiatry

“This line of work is moving the field one step closer to precision psychiatry,” Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Massachusetts, said in an interview.

“Outside of psychiatry, many diseases have measurable biomarkers that correlate with whether the disease is present or its severity. For example, for diabetes there is hemoglobin A1c, and for multiple sclerosis, brain lesions on MRI are both diagnostic and prognostic. Sadly, within psychiatry, biomarkers are few and far between,” said Dr. Lakhan, who wasn’t involved in this study.

“Over the last decades, an interesting phenomenon occurs with DBS for patients with advanced Parkinson’s – often their depression abates and mood improves. Several lines of studies have tried to tease apart whether this was primarily from alleviating the motor symptoms of Parkinson’s or [if] DBS is directly implicated in mood enhancement. Lo and behold a subset of patients with treatment-resistant depression demonstrate improvement on standardized depression testing,” Dr. Lakhan added.

This study now shows that beta rhythm – a signal deep in the brain that traditional EEG can’t pick up – “predicted who would later benefit from DBS right at the time of implantation,” Dr. Lakhan said.

“This is incredibly important for not only predicting response to DBS for depression, but specifically targeting this potential biomarker (deep beta rhythm) in and outside of brain surgery,” he told this news organization.

“Other therapy trials, for instance, with drugs or non-invasive, digital neuroactivation and modulation (DiNaMo), may use this key biomarker to optimize its development and maximize effect, one day, for a given individual,” Dr. Lakhan predicted.

“The challenge remains that these signals are deep in the brain and currently require surgical implantation of electrodes for recordings. However, technologies such as magnetoencephalography (MEG) that use powerful external magnetics may substitute,” he added.

Funding support was provided by the National Institutes of Health, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Hope for Depression Research Foundation. Implanted devices used in this research were donated by Medtronic. Dr. Mayberg receives consulting and licensing fees from Abbott Labs. Dr. Lakhan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

He always dressed the same at conferences: dark suit, white shirt, bright red bow tie.

Courtesy of Beck Institute for Cognitive Behavior Therapy

For all his fame, he was very kind, warmly greeting those who wanted to see him and immediately turning attention toward their research rather than his own. Aaron Beck actually didn’t lecture much; he preferred to roleplay cognitive therapy with an audience member acting as the patient. He would engage in what he called Socratic questioning, or more formally, cognitive restructuring, with warmth and true curiosity:

• What might be another explanation or viewpoint?
• What are the effects of thinking this way?
• Can you think of any evidence that supports the opposite view?

The audience member/patient would benefit not only from thinking about things differently, but also from the captivating interaction with the man, Aaron Temkin Beck, MD, (who went by Tim), youngest child of Jewish immigrants from the Ukraine.

When written up in treatment manuals, cognitive restructuring can seem cold and overly logical, but in person, Dr. Beck made it come to life. This ability to nurture curiosity was a special talent; his friend and fellow cognitive psychologist Donald Meichenbaum, PhD, recalls that even over lunch, he never stopped asking questions, personal and professional, on a wide range of topics.

It is widely accepted that Dr. Beck, who died Nov. 1 at the age of 100 in suburban Philadelphia, was the most important figure in the field of cognitive-behavioral therapy (CBT).

He didn’t invent the field. Behaviorism predated him by generations, founded by figures such as John Watson and B.F. Skinner. Those psychologists set up behaviorism as an alternative to the reigning power of Freudian psychoanalysis, but they ran a distant second.

It wasn’t until Dr. Beck added a new approach, cognitive therapy, to the behavioristic movement that the new mélange, CBT, began to gain traction with clinicians and researchers. Dr. Beck, who had trained in psychiatry, developed his ideas in the 1960s while observing what he believed were limitations in the classic Freudian methods. He recognized that patients had “automatic thoughts,” not just unconscious emotions, when they engaged in Freudian free association, saying whatever came to their minds.

These thoughts often distorted reality, he observed; they were “maladaptive beliefs,” and when they changed, patients’ emotional states improved.

Dr. Beck wasn’t alone. The psychologist Albert Ellis, PhD, in New York, had come to similar conclusions a decade earlier, though with a more coldly logical and challenging style. The prominent British psychologist Hans Eysenck, PhD, had argued strongly that Freudian psychoanalysis was ineffective and that behavioral approaches were better.

Dr. Beck turned the Freudian equation around: Instead of emotion as cause and thought as effect, it was thought which affected emotion, for better or worse. Once you connected behavior as the outcome, you had the essence of CBT: thought, emotion, and behavior – each affecting the other, with thought being the strongest axis of change.

The process wasn’t bloodless. Behaviorists defended their turf against cognitivists, just as much as Freudians rejected both. At one point the behaviorists in the Association for the Advancement of Behavior Therapy tried to expel the advocates of a cognitive approach. Dr. Beck responded by leading the cognitivists in creating a new journal; he emphasized the importance of research being the main mechanism to decide what treatments worked the best.

Putting these ideas out in the 1960s and 1970s, Dr. Beck garnered support from researchers when he manualized the approach. Freudian psychoanalysis was idiosyncratic; it was almost impossible to study empirically, because the therapist would be responding to the unpredictable dreams and memories of patients engaged in free association. Each case was unique.

But CBT was systematic: The same general approach was taken to all patients; the same negative cognitions were found in depression, for instance, like all-or-nothing thinking or overgeneralization. Once manualized, CBT became the standard method of psychotherapy studied with the newly developed method of randomized controlled trials (RCTs).

By the 1980s, RCTs had proven the efficacy of CBT in depression, and the approach took off.

Dr. Beck already had developed a series of rating scales: the Beck Depression Inventory, the Beck Scale for Suicidal Ideation, the Beck Anxiety Inventory, the Beck Hopelessness Scale. Widely used, these scales extended his influence enormously. Copyrighted, they created a new industry of psychological research.

Dr. Beck’s own work was mainly in depression, but his followers extended it everywhere else: anxiety disorders and phobias, eating disorders, substance abuse, bipolar illness, even schizophrenia. Meanwhile, Freudian psychoanalysis fell into a steep decline from which it never recovered.

Dr. Beck’s CBT became king of the hill in psychotherapy, but it wasn’t without criticism.

Some argued that it was abetted by insurance restrictions on psychotherapy, which favored shorter-term CBT; others that its research was biased in its favor because psychotherapy treatments, unlike medications, cannot be blinded; others that its efficacy could not be shown to be specific to its theory, as opposed to the interpersonal relationship between therapist and client.

Still, CBT has transformed psychotherapy and continues to expand its influence. Computer-based CBT has been proven effective, and digital CBT has become a standard approach in many smartphone applications and is central to the claims of multiple new biotechnology companies advocating for digital psychotherapy.

Aaron Beck continued publishing scientific articles to age 98. His last papers reviewed his life’s work. He characteristically gave credit to others, calmly recollected how he traveled away from psychoanalysis, described how his work started and ended in schizophrenia, and noted that the “working relationship with the therapist” remained a key factor for the success of CBT.

That parting comment reminds us that behind all the technology and research stands the kindly man in the dark suit, white shirt, and bright red bow tie, looking at you warmly, asking about your thoughts, and curiously wondering what might be another explanation or viewpoint you hadn’t considered.
 

Nassir Ghaemi, MD, MPH, is a professor of psychiatry at Tufts Medical Center and a lecturer in psychiatry at Harvard Medical School. He is the author of several general-interest books on psychiatry. A version of this article first appeared on Medscape.com.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Universal screening for adolescent depression in schools, compared with the usual process of targeting students for referral after observing behaviors, resulted in significantly higher odds of identifying major depressive disorder (MDD) and of starting treatment for it, a study of more than 12,000 students suggests. Findings were published online in JAMA Network Open.

Deepa L. Sekhar, MD, MSc, with the department of pediatrics at Pennsylvania State College of Medicine in Hershey, Pa., and colleagues conducted a randomized clinical trial comparing the two screening methods from November 2018 to November 2020.

The trial included students in grades 9 through 12 enrolled at any of the 14 participating Pennsylvania public high schools. Researchers compared the two groups using mixed-effects logistic regression.

They found that adolescents in the universal screening intervention group had 5.92 times higher odds (95% confidence interval [CI], 5.07-6.93) of being identified with MDD symptoms, 3.30 times higher odds (95% CI, 2.49-4.38) of the Student Assistance Program (SAP) confirming follow-up needs, and 2.07 times higher odds (95% CI, 1.39-3.10) of starting MDD treatment.

The study comprised 12,909 students, with an average age of 16 years. Of those students, 2,687 (20.8%) were Hispanic; 2,891 (22.4%) were non-Hispanic Black, 5,842 (45.3%) were non-Hispanic White; and 1,489 (11.5%) were multiracial or of other race or ethnicity.

In the universal screening intervention (n = 6,473) all students completed the Patient Health Questionnaire–9 (PHQ-9). Students who screened positive proceeded to the Student Assistance Program. Students could receive a targeted referral to SAP if they had concerning behavior beyond the PHQ-9.

In the targeted screening group (n = 6,436), students with behaviors prompting concern for MDD were referred to the Student Assistance Program (SAP), mandated in all Pennsylvania schools. The SAP determined follow-up.

The U.S. Preventive Services Task Force (USPSTF) endorsed primary care screening in 2009 and again in 2016 for all adolescents 12-18 years old.

However, the study authors wrote, most U.S. adolescents (more than 60%) don’t have routine access to preventive health care, which limits primary care offices’ ability to properly address the growing numbers.

“[S]creening is inconsistent, with inequalities by race and ethnicity and region, and potential worsening with the COVID-19 pandemic,” they noted.

Depression rates see sharp increase

Meanwhile, the prevalence of adolescents reporting MDD symptoms has “nearly doubled in the last decade, increasing from 8.3% in 2008 to 14.4% in 2018.”

The American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and Children’s Hospital Association recently declared a national emergency in children’s mental health, citing COVID-19’s toll on top of existing challenges.

This study provides further evidence that universal screening is the better approach to identify and treat adolescent depression to save lives, Andres Pumariega, MD, a child and adolescent psychiatrist at University of Florida in Gainesville, told this news organization.

“If you catch these kids early, you can prevent suicide attempts and suicide. You can also prevent complicating costs of care,” he said.

He noted the universal screening removes the potential for bias.

“Relying purely on referral and clinical identification means a lot of kids in minority groups will not be identified and will not be treated accurately. Many clinicians have a problem identifying depression in diverse kids,” he said.

Pushback for universal screening likely

However, he said he has been part of such efforts to implement such programs in Mexico and the United States and said in the Unites States, the political climate will guarantee pushback from having schools more involved in health care and prevention. Recent controversy around COVID-19 vaccines for children illustrates the potential backlash, he said.

Parents often fight such programs as attempts to “label” their children, he said.

“If I have cancer, I sure want to be labeled. A label is used to get them help. We need to find ways to educate parents and support them in facing these issues,” he added.

One concern he has with this intervention is having the SAPs, composed largely of nonclinicians, be the triage point “instead of doing that objectively through objective criteria and by clinicians,” he said. “If we are to have a comprehensive health system where we can serve all kids and manage costs, schools need to be a major part of it.”

School settings offer the chance to see more children, collaborate with teachers and counselors, and integrate results with educational outcomes, he added.

In the study by Sekhar and colleagues, 7 of the 14 schools were classified as urban, with a median size of 370 students.

Researchers noted that the benefit of the universal screening is likely understated because of COVID-19–related school closures during the study period. The closures meant screening wasn’t completed for 7% of students.

The authors concluded that universal screening finds teens living with depression who otherwise would not be found. They said such a program likely works best in schools with strong SAP.

“Adolescents’ consistent contact with schools has been used to support physical health screenings that affect academic success,” the authors wrote. “Major depressive disorder similarly affects academic success, suggesting school-based screening may be especially beneficial.”

In the past 3 years, Dr. Sekhar reported receiving funding from Pfizer through the American Academy of Pediatrics, the Penn State Clinical and Translational Science Awards Program, and a Eugene Washington Patient-Centered Outcomes Research Institute Engagement Award. Full disclosures for coauthors are available in the journal article.

This work was supported in part by the Patient-Centered Outcomes Research Institute. The use of REDCap (Research Electronic Data Capture) in this project was supported by the National Institutes of Health.

Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.

On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.

“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.

For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT_2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.

Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.

Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.

However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.

“Psychiatric disorders are syndromes, categorized by a collection of symptoms defined descriptively but not neurobiologically,” Dr. Stahl said. Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.

To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .

“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.

He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.

“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.

So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.

Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT₂ antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.

“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.

While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.

“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.

The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.

“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
 

Agency’s arbitrary decisions cited

“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.

In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.

Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”

“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.

Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.

Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.

On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.

“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.

For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT_2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.

Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.

Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.

However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.

“Psychiatric disorders are syndromes, categorized by a collection of symptoms defined descriptively but not neurobiologically,” Dr. Stahl said. Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.

To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .

“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.

He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.

“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.

So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.

Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT₂ antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.

“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.

While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.

“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.

The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.

“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
 

Agency’s arbitrary decisions cited

“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.

In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.

Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”

“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.

Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.

Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.

If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.

On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.

“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.

For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT_2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.

Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.

Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.

However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.

“Psychiatric disorders are syndromes, categorized by a collection of symptoms defined descriptively but not neurobiologically,” Dr. Stahl said. Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.

To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .

“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.

He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.

“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.

So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.

Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT₂ antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.

“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.

While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.

“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.

The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.

“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
 

Agency’s arbitrary decisions cited

“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.

In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.

Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”

“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.

Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.

There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There are multiple benefits and few harms from sharing clinical notes in patients with mental illness, results of a poll of international experts show.

As of April 5, 2021, new federal rules in the United States mandate that all patients are offered online access to their electronic health record. 

“Given that sharing notes in psychiatry is likely to be more complicated than in some other specialties, we were unsure whether experts would consider the practice more harmful than beneficial,” Charlotte Blease, PhD, of Beth Israel Deaconess Medical Center in Boston, told this news organization.

“However, the results of our poll suggest clinicians’ anxieties about sharing mental health notes with patients may be misplaced. We found clear consensus among experts that the benefits of online access to clinical notes could outweigh the risks,” Dr. Blease said in a news release.

The study was published online in PLOS ONE.

Empowering patients

Investigators used an online Delphi poll, an established methodology used to investigate emerging health care policy – including in psychiatry – to solicit the views of an international panel of experts on the mental health effects of sharing clinical notes.

The panel included clinicians, chief medical information officers, patient advocates, and informatics experts with extensive experience and research knowledge about patient access to mental health notes.

There was consensus among the panel that offering online access to mental health notes could enhance patients’ understanding about their diagnosis, care plan, and rationale for treatments.

There was also consensus that access to clinical notes could enhance patient recall about what was communicated and improve mental health patients’ sense of control over their health care.

The panel also agreed that blocking mental health notes could lead to greater harms including increased feelings of stigmatization.

Confirmatory findings

The poll results support an earlier study by Dr. Blease and colleagues that evaluated the experiences of patients in accessing their online clinical notes. 

Among these patients with major depressive disorder, schizophrenia, schizoaffective disorder, or bipolar-related disorder, “access helped to clarify why medications had been prescribed, improved understanding about side effects, and 20% of patients reported doing a better job taking their meds as prescribed,” said Dr. Blease.

However, the expert panel in the Delphi poll predicted that with “open notes” some patients might demand changes to their clinical notes, and that mental health clinicians might be less detailed/accurate in documenting negative aspects of the patient relationship, details about patients’ personalities, or symptoms of paranoia in patients.

“If some patients feel more judged or offended by what they read, this may undermine the therapeutic relationship. We also need more research into the experiences of patients hospitalized for their care,” she added.

“In some clinical cases where there is more focus on emergency care than in forming a therapeutic relationship, for example emergency department visits, we know almost nothing about the risks and benefits associated with OpenNotes,” senior author John Torous, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, said in an interview.

“One thing is clear,” Dr. Blease said. “Patient access to their online medical records is now mainstream, and we need more clinician education on how to write notes that patients will read, and more guidance among patients on the benefits and risks of accessing their notes.”

Support for this research was provided by a J. F. Keane Scholar Award and a Swedish Research Council on Health, Working Life, and Welfare grant. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

The antidepressant fluvoxamine (Luvox) may prevent hospitalization and death in outpatients with COVID-19, new research suggests.

HconQ/ThinkStock

Results from the placebo-controlled, multisite, phase 3 TOGETHER trial showed that in COVID-19 outpatients at high risk for complications, hospitalizations were cut by 66% and deaths were reduced by 91% in those who tolerated fluvoxamine.

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population,” wrote the investigators, led by Gilmar Reis, MD, PhD, research division, Cardresearch, Belo Horizonte, Brazil.

The findings were published online Oct. 27 in The Lancet Global Health.
 

Alternative mechanisms

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is an antidepressant commonly prescribed for obsessive-compulsive disorder.

Besides its known effects on serotonin, the drug acts in other molecular pathways to dampen the production of inflammatory cytokines. Those alternative mechanisms are the ones believed to help patients with COVID-19, said coinvestigator Angela Reiersen, MD, child psychiatrist at Washington University, St. Louis.

Based on cell culture and mouse studies showing effects of the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, Dr. Reiersen came up with the idea of testing if fluvoxamine could keep COVID-19 from progressing in newly infected patients.

Dr. Reiersen and psychiatrist Eric Lenze, MD, also from Washington University, led the phase 2 trial that initially suggested fluvoxamine’s promise as an outpatient medication. They are coinvestigators on the new phase 3 adaptive platform trial called TOGETHER, which was conducted by an international team of investigators in Brazil, Canada, and the United States.

For this latest study, researchers at McMaster University, Hamilton, Ont., partnered with the research clinic Cardresearch in Brazil to recruit unvaccinated, high-risk adults within 7 days of developing flu-like symptoms from COVID-19. They analyzed 1,497 newly symptomatic COVID-19 patients at 11 clinical sites in Brazil.

Patients entered the trial between January and August 2021 and were assigned to receive 100 mg fluvoxamine or placebo pills twice a day for 10 days. Investigators monitored participants through 28 days post treatment, noting whether complications developed requiring hospitalization or more than 6 hours of emergency care.

In the placebo group, 119 of 756 patients (15.7%) worsened to this extent. In comparison, 79 of 741 (10.7%) fluvoxamine-treated patients met these primary criteria. This represented a 32% reduction in hospitalizations and emergency visits.
 

Additional analysis requested

As Lancet Global Health reviewed these findings from the submitted manuscript, journal reviewers requested an additional “pre-protocol analysis” that was not specified in the trial’s original protocol. The request was to examine the subgroup of patients with good adherence (74% of treated group, 82% of placebo group).

Among these three quarters of patients who took at least 80% of their doses, benefits were better.

Fluvoxamine cut serious complications in this group by 66% and reduced mortality by 91%. In the placebo group, 12 people died compared with one who received the study drug.

Based on accumulating data, Dr. Reiersen said, some experts are recommending fluvoxamine for COVID-19 patients at high risk for morbidity and mortality from complications of the infection.

However, clinicians should note that the drug can cause side effects such as nausea, dizziness, and insomnia, she added. In addition, because it prevents the body from metabolizing caffeine, patients should limit their daily intake to half of a small cup of coffee or one can of soda or one tea while taking the drug.

Previous research has shown that fluvoxamine affects the metabolism of some drugs, such as theophylline, clozapine, olanzapine, and tizanidine.

Despite huge challenges with studying generic drugs as early COVID-19 treatment, the TOGETHER trial shows it is possible to produce quality evidence during a pandemic on a shoestring budget, noted co-principal investigator Edward Mills, PhD, professor in the department of health research methods, evidence, and impact at McMaster University.

To screen more than 12,000 patients and enroll 4,000 to test nine interventions, “our total budget was less than $8 million,” Dr. Mills said. The trial was funded by Fast Grants and the Rainwater Charitable Foundation.
 

‘A $10 medicine’

Commenting on the findings, David Boulware, MD, MPH, an infectious disease physician-researcher at the University of Minnesota in Minneapolis, noted fluvoxamine is “a $10 medicine that’s available and has a very good safety record.”

By comparison, a 5-day course of Merck’s antiviral molnupiravir, another oral drug that the company says can cut hospitalizations in COVID-19 outpatients, costs $700. However, the data have not been peer reviewed – and molnupiravir is not currently available and has unknown long-term safety implications, Dr. Boulware said.

Pharmaceutical companies typically spend tens of thousands of dollars on a trial evaluating a single drug, he noted.

In addition, the National Institutes of Health’s ACTIV-6 study, a nationwide trial on the effect of fluvoxamine and other repurposed generic drugs on thousands of COVID-19 outpatients, is a $110 million effort, according to Dr. Boulware, who cochairs its steering committee.

ACTIV-6 is currently enrolling outpatients with COVID-19 to test a lower dose of fluvoxamine, at 50 mg twice daily instead of the 100-mg dose used in the TOGETHER trial, as well as ivermectin and inhaled fluticasone. The COVID-OUT trial is also recruiting newly diagnosed COVID-19 patients to test various combinations of fluvoxamine, ivermectin, and the diabetes drug metformin.

Unanswered safety, efficacy questions

In an accompanying editorial in The Lancet Global Health, Otavio Berwanger, MD, cardiologist and clinical trialist, Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil, commends the investigators for rapidly generating evidence during the COVID-19 pandemic.

However, despite the important findings, “some questions related to efficacy and safety of fluvoxamine for patients with COVID-19 remain open,” Dr. Berwanger wrote.

The effects of the drug on reducing both mortality and hospitalizations also “still need addressing,” he noted.

“In addition, it remains to be established whether fluvoxamine has an additive effect to other therapies such as monoclonal antibodies and budesonide, and what is the optimal fluvoxamine therapeutic scheme,” wrote Dr. Berwanger.

In an interview, he noted that 74% of the Brazil population have currently received at least one dose of a COVID-19 vaccine and 52% have received two doses. In addition, deaths have gone down from 4,000 per day during the March-April second wave to about 400 per day. “That is still unfortunate and far from ideal,” he said. In total, they have had about 600,000 deaths because of COVID-19.

Asked whether public health authorities are now recommending fluvoxamine as an early treatment for COVID-19 based on the TOGETHER trial data, Dr. Berwanger answered, “Not yet.

“I believe medical and scientific societies will need to critically appraise the manuscript in order to inform their decisions and recommendations. This interesting trial adds another important piece of information in this regard,” he said.

Dr. Reiersen and Dr. Lenze are inventors on a patent application related to methods for treating COVID-19, which was filed by Washington University. Dr. Mills reports no relevant financial relationships, as does Dr. Boulware – except that the TOGETHER trial funders are also funding the University of Minnesota COVID-OUT trial. Dr. Berwanger reports having received research grants outside of the submitted work that were paid to his institution by AstraZeneca, Bayer, Amgen, Servier, Novartis, Pfizer, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.